In the last few decades, the development of new drugs that have much more potency has been a primary focus in the pharmaceutical field. However, the administration of such drugs has been limited due to poor absorption and enzymatic degradation in the gastrointestinal tract as well as painful delivery using intravascular injection. One feasible solution to solve these problems is by administering those drugs across the skin using a patch, although its therapeutic rates are very limited due to skin permeability. In recent years, substantial effort has been spent to overcome this difficulty by incorporating skin permeation enhancer, electric field, ultrasound, and microneedles in the drug delivery systems. Among these approaches, the use of microneedles appears most promising since they can provide holes to bypass the stratum corneum of a patient's skin with little or no pain.
Microneedles, especially when arranged in arrays, find use in obtaining biological fluid samples and for delivering drugs, agents, formulations or biological molecules across biological tissue barriers. The microneedles used for delivering one or more compounds may be categorized as luminal or dissolvable. Dissolvable microneedles include a polymer tip that dissolves when in contact with body fluid to deliver a drug, vaccine inoculation, or other therapeutic agent. As the designation implies, luminal microneedles are bodies that include a lumen therein.
The lumen in this class of microneedle may be used to deliver compounds (especially in connection with various reservoir means such as described in U.S. Pat. No. 3,964,482 or 8,257,324). Alternatively, the lumen may be used for analyte collection, in which case, an array of microneedles may be combined with analyte measurement systems to provide a minimally invasive fluid retrieval and analyte sensing system such as described in U.S. Pat. No. 6,749,792. Notable analytes of interest obtained from biological fluids include glucose and cholesterol.
Microneedles are sometimes made from stainless steel or other metals. Metal needles are subject to numerous disadvantages. Some of these include the manufacturing complexities associated with wire drawing, grinding, deburring, and clean-up steps of the manufacturing process. Further, impurities in the metals can cause oxidation and deterioration of the needles. Further examples of microneedle fabrication approaches include employing photolithography and electroplating. Ultimately, silicon-based or stainless steel-based microneedles are not attractive due to their high material and fabrication cost.
Other microneedles are fabricated employing micro-replication techniques, such as injection molding of a plastic material or the like. Such approaches enable a degree of design flexibility and cost savings.
However, the resulting products of all of the aforementioned fabrication techniques fail to offer many of the advantages associated with microneedles and microneedle arrays fabricated from carbon nanotubes (CNTs). CNT-based microneedles have unmatched advantages due to their exceptional mechanical properties and simple fabrication process. Regarding ease of fabrication, they may be produced in large quantity by self-assembly to form a nanotube “carpet” of columns or pillars through chemical vapor deposition (CVD) or such other processes as described in U.S. Pat. No. 7,491,628 or US Publication Nos. 2003/0180472, 2008/0145616 or 2010/0247777. As to physical properties important to microneedle fabrication (aside from size in a relevant range), CNT-based microneedles offer superb column strength (i.e., an ability to withstand a compression load of at least 80 MPa), flexibility (as a measure of toughness against inadvertent damage in handling), and high aspect ratio.
In order to achieve such advantages, however, the so-called carpet of CNT pillars must be processed further in order to configure a workable microneedle array. Suitable processing techniques and the resulting array structures are described in U.S. Pat. No. 7,955,644 and US Publications 2010/0196446, 2012/0021164 and 2012/0058170—all assigned to California institute of Technology (the assignee hereof) and all (together with their foreign counterparts) incorporated herein by reference in their entireties for all purposes. Moreover, such arrays may be further processed to produce superhydrophobic CNT arrays as described in US Publication No. 2011/0250376 (also to the assignee hereof and incorporated by reference herein in its entirety) through vacuum pyrolysis.
Different forms of improvement to such devices (e.g., as described in any U.S. Pat. No. 7,955,644 and US Publications 2010/0196446, 2011/0250376, 2012/0021164 and 2012/0058170) or other CNT microneedles or microneedle arrays are described herein.